The role of the neuropathology core will be to: 1) supervise and monitor the acquisition of brain tissue from patients 50 to 100 years of age who die and are brought into the Project and 2) undertake the neuropathological analysis of these cases. More specifically, we will: 1) establish a diagnosis of Alzheimer's disease (AD) in 75 brains and identify 45 normal control brains, excluding patients with other neuropathologic processes; 2) quantify the topographic extent of classical AD changes (neurons with neurofibrillary tangles (NFT) and neuritic plaques (NP)) in neocortex and hippocampus in all cases; and 3) perform rigorous, layer-by-layer counts of NFT and NP in the cortical areas selected by members of the Project group: middle frontal gyrus (MFG, Brodmann's Areas 9 or 46), superior temporal gyrus (STG, Brodmann's Area 22) and entorhinal cortex (ENT, Brodmann's Area 28). Counts will also be made in hippocampus (CA-1) in each case. These changes will then be compared with changes in dendritic arbors (Project 1), the loss or shrinkage of cortical neurons (Projects 2 and 3), and local cholinergic and noradrenergic markers (Projects 3 and 4) in the same areas; and changes in the cells of origin for the ascending cholinergic and noradrenegic projection to those areas, nucleus basalis and locus coeruleus. Thus, NP and NFT densities will represent an index of the "severity" of AD involvement in each area studied.